Modeling Influenza Antiviral Strategies: Reducing Burden and Preventing Resistance.

Annually, influenza epidemics lead to hundreds of thousands of deaths worldwide many more hospitalizations. The antivirals baloxavir and oseltamivir improve outcomes and limit virus spread, but their widespread use may accelerate the emergence of drug-resistant influenza variants, particularly in young children. Using a data-driven model, we assess various age-stratified antiviral treatment strategies, in terms of reducing both illness and the risk of resistance. In a typical influenza season in the United States, administering baloxavir to 20% of symptomatic individuals >5 years old would be expected to reduce the median disability-adjusted life-years (DALYs) lost by 32.3%, but with a 26.4% risk of resistance transmitting widely. If those patients instead received oseltamivir, DALYs lost would decrease by 19.5%, with only a 5.4% chance of widespread resistance. Strategies such as suspending baloxavir use on detection of resistance or administering combination baloxavir-oseltamivir therapy could further mitigate these risks. For example, treating the same patient population with combination therapy would achieve a 33.5% reduction in DALYs lost, with a 10.2% likelihood of baloxavir resistance emergence and community transmission.